ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6551G>C (p.Ser2184Thr) (rs374551964)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216780 SCV000274678 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Color RCV000216780 SCV000687709 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing
GeneDx RCV000159748 SCV000209763 uncertain significance not provided 2014-04-22 criteria provided, single submitter clinical testing This variant is denoted ATM c.6551G>C at the cDNA level, p.Ser2184Thr (S2184T) at the protein level, and results in the change of a Serine to a Threonine (AGC>ACC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Ser2184Thr was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Serine and Threonine share similar properties, this is considered a conservative amino acid substitution and is unlikely to affect protein integrity. ATM Ser2184Thr occurs at a position that is highly variable across species and is located in the FAT domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether ATM Ser2184Thr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000227041 SCV000283021 uncertain significance Ataxia-telangiectasia syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 2184 of the ATM protein (p.Ser2184Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs374551964, ExAC 0.001%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 181980). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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